Compositions and methods for treatment of prediabetes

ABSTRACT

The invention provides compositions and methods to treat prediabetes. In particular, the invention has discovered that particular combinations of diverse types of antioxidants have synergistic and surprising effects for use against prediabetes. The diverse types of antioxidants include: antioxidants that comprise stabilizing heteroatoms; antioxidants with conjugated segments of alternating single and double bonds; antioxidants with disulfides; and antioxidants with phenolic groups. In particularly useful embodiments one or more of the antioxidants that comprise stabilizing heteroatoms have pro-oxidant effects, e.g., in the liver.

FIELD OF THE INVENTION

The invention concerns compositions and methods for the treatment andprevention of prediabetes.

BACKGROUND

Prediabetes is a condition characterized by abnormally high yet lessthan extreme blood sugar levels, (i.e., in the range of 100 to 125mg/dL). Prediabetic patients lack one or more symptoms that characterizediabetes, however but the condition is often a prelude to type 2diabetes mellitus (T2DM). A quarter of the cases commonly progress toT2DM within 3 to 5 years, and half within 10 years. Prediabetes may beidentical to metabolic syndrome, however the latter is evaluated by adifferent set of biomarkers.

A common symptom of prediabetes is impaired fasting glucose (IFG), inwhich blood sugar levels are high but still below those typical ofdiabetes. Many IFG patients retain normal responses to a glucosetolerance test. Another common system is impaired glucose tolerance(IGT) associated with insulin resistance and elevated cardiovascularrisk. Among American adults over 40 years of age, 33% have IFG, 15% haveIGT, and 40% are prediabetic (i.e., they have IFG and/or IGT).

Despite those diagnostic conditions the symptoms of prediabetes areoften not distinctive. Thus a range of signs are monitored: persistenthunger; obesity; weight gain or at the other extreme, unexplained weightloss; flu-like weakness and fatigue; blurry vision; slowness of healingfor cuts and bruises; tingling or insensate extremities; and recurringinfections of the skin, gums, bladder or vagina.

Prediabetes is associated with many possible causes beyond high bloodsugar, and these range from sleep disorders, genetics, cardiovasculardisease, hypertension, high triglyceride levels, low HDL cholesterol,elevated weight, pregnancy, high birth weight, polycystic ovariansyndrome.

The lifestyle intervention guidelines to prevent the onset of type 2diabetes include: dietary regimes that are low in sugar, refinedcarbohydrates, saturated fats, salt and total calories; regular physicalexercise, for instance 30 minutes per day five days per week; and weightreduction even by as little as a few percent.

The prevalence of prediabetes remains high despite widespread medicalmonitoring and health education, and methods to treat it have beenlacking apart from the lifestyle changes just discussed. Consequentlythere is an ongoing need for compositions to treat and prevent 5prediabetes.

SUMMARY OF THE INVENTION

The invention provides compositions and methods to treat and preventdevelopment of prediabetes. In particular, the present invention hasdiscovered that particular combinations of 10 diverse types ofantioxidants that have synergistic and surprising effects for useagainst prediabetes. The diverse types of antioxidants include:antioxidants that comprise stabilizing heteroatoms; antioxidants withconjugated segments, i.e., segments in which double bonds alternate withsingle bonds; antioxidants with disulfide bonds; and antioxidants withphenolic groups. It has further been discovered that it is beneficial touse antioxidants that facilitate an oxidative balance, i.e., that havepro-oxidant effects, e.g., in the liver.

Particularly suitable compositions for the invention include acombination of each of the ingredients indicated in Table I.

TABLE I Taurine in a range of 40-360 mg; a non- limiting illustrativequantity is 200 mg. Taurine is an antioxidant that comprises astabilizing heteroatom, relieves oxidative stress, and has apro-oxidative effect in the liver.

Beta-alanine in a range of 10-90 mg; a non- limiting illustrativequantity is 50 mg. Beta- alanine is an anti oxidant that comprises astabilizing heteroatom.

Acetyl-L-carnitine in a range of 20-180 mg; a non-limiting illustrativequantity is 100 mg. Acetyl-L-carnitine is an antioxidant that comprisesa stabilizing heteroatom, relieves oxidative stress, and has apro-oxidative effect in the liver.

Agmatine in a range of 25-225 mg; a non- limiting illustrative quantityis 125 mg. Agmatine is an antioxidant that comprises a stabilizingheteroatom.

Grape seed extract in a range of 10-90 mg; a non-limiting illustrativequantity is 50 mg. Grape seed extract comprises phenolic antioxidants,such as for instance, (−)- epicatechin and oligomers of (−)-epicatechin.

L-carnosine in a range of 5-45 mg; a non- limiting illustrative quantityis 25 mg. L- carnosine is an antioxidant that comprises a stabilizingheteroatom, and is active against reactive organic species (ROS)radicals.

Vitamin D3 in a range of 500-4500 I.U.; a non-limiting illustrativequantity is 2500 I.U. Vitamin D3 is an antioxidant with conjugatedhydrocarbon segments.

Methylcobalamin (a form of Vitamin B12), 20-220 μg; a non-limitingillustrative quantity is 120 μg. Methylcobalamin is an antioxidant thatcomprises a conjugated segment; the segment contains nitrogen atoms andamong other properties can bind the oxidant nitric oxide (NO).

Methylcobalamin

In particular embodiments compositions of the invention include acombination of each of the ingredients indicated in both Tables I andII.

TABLE II

Alpha-Lipoic Acid in a range of 50-450 μg; a non-limiting illustrativequantity is 500 μg. Alpha-Lipoic Acid is a disulfide-type antioxidant

The embodiments of the invention as described herein are merelyillustrative and are not exclusive. Numerous additions, variations,derivations, permutations, equivalents, combinations and modificationsof the above-described invention will be apparent to persons of ordinaryskill in the relevant arts and are within the scope and spirit of theinvention. The invention as described herein contemplates the use ofthose alternative embodiments without limitation.

The invention claimed is:
 1. A method for treatment of prediabetescomprising administration of a composition comprising taurine,beta-alanine, acetyl-L-carnitine, agmatine and L-carnosine; b) at leastone of the antioxidant compounds selected from the group consisting ofvitamin D compounds, cobalamin compounds and carotenoids; c) at leastone of the antioxidant compounds selected from the group consisting ofalpha-lipoic acid; and d) at least one of the antioxidant compoundsselected from the group consisting of epicatechin and oligomers ofepicatechin; wherein: the amount of the composition is effective toreduce or mitigate at least one symptom of prediabetes.
 2. The method ofclaim 1 wherein the antioxidant b) consists of vitamin D3,methylcobalamin, and lutein.
 3. The method of claim 1 whereinepicatechin and the oligomers of epicatechin are provided in the form ofgrape seed extract.
 4. The method of claim 1 wherein the compositioncomprises: a) taurine in an amount selected from the range of 40 to 360mg; b) beta-alanine in an amount selected from the range of 10 to 90 mg;c) acetyl-L-carnosine in an amount selected from the range of 20 to 180mg; d) agmatine in an amount selected from the range of 25 to 225 mg; e)grape seed extract in an amount selected from the range of 10 to 90 mg;f) L-carnosine in an amount selected from the range of 5 to 45 mg; g)vitamin D3 in an amount selected from the range of 500 to 4,500 I.U.;and h) methylcobalamin in an amount selected from the range of 20 to 220μg.
 5. The method of claim 1 wherein the composition further comprises:a) lutein in an amount selected from the range of 1 to 9 mg; and b)alphalipoic acid in an amount selected from the range of 100 to 900 μg.6. The method of claim 1 wherein the composition comprises: a) taurinein an amount of 200 mg; b) beta-alanine in an amount of 50 mg; c)acetyl-L-carnosine in an amount of 100 mg; d) agmatine in an amountselected of 125 mg; e) grape seed extract in an amount of 50 mg; f)L-carnosine in an amount of 25 mg; g) vitamin D3 in an amount of 2,500I.U.; h) methylcobalamin in an amount of 120 μg; i) lutein in an amountof 5 mg; and j) alphalipoic acid in an amount of 500 μg.